The present invention relates to a process for the production of dihydroketoisophorone (DH-KIP; 2,2,6-trimethylcyclohexane-1,4-dione) by epoxidation of xcex2-isophorone with a percarboxylic acid solution in an inert, non-water-soluble solvent, which is, at the same time, the solvent used for epoxidation: of xcex2-isophorone (xcex2-IP) to xcex2-isophorone epoxide (xcex2-IPO) and subsequent isomerization to 4-hydroxyisophorone (HIP) and the product DH-KIP. In particular, an industrially advantageous process is provided, in which the reaction sequence: epoxidation, ring opening of the epoxide to HIP and isomerization of HIP to the product takes place in a pH range which allows the entire synthesis sequence to be carried selectively without the need for frequent changes from acid to basic condition.
In particular, an advantageous process is described, in which all reactions can be carried out one after the other in one reaction unit, without the need for intermediate isolation of discharged intermediates.
The DH-KIP obtained from this process can be converted directly to trimethylhydroquinonediacetate (TMHQ-DA) by oxidative aromatization. Trimethylhydroquinonediacetate is a central educt of vitamin E acetate synthesis. DH-KIP is also an important component for various carotinoid syntheses. In addition to its uses in the human sphere, vitamin E acetate is used in the form of special formulations as an additive for animal feed.
3,5,5-trimethyl-4-hydroxy-cyclohex-2-en-1-one (HIP) is described in the literature as a flavoring and aromatizing substance (JP-81 35 990; CH 549 961; DE 22 02 066). Its use as a food flavoring is also known (CH 549 956; M. Ishikara et al., J.Org. Chem. 1986, 51, 491 et seq.). HIP also has a variety of applications as a synthetic component for natural products and various pharmaceuticals (N. S. Zarghami et al., Phytochemistry 1971, 10, 2755 et seq.; J. N. Marx and F. Sondheimer, Tetrahedron Lett., Suppl. No. 8, Pt 1, 1-7, 1966). In particular xcex2-IPO is an important intermediate for the synthesis of 2,6,6-trimethylcyclohexane-1,4-dione and thus for vitamin E. The conventional synthesis sequence is as follows: 
The known processes for the production of xcex2-IPO produce only unsatisfactory yields. It was found that oxidation of xcex2-isophorone normally proceeds to 4-oxo-isophorone, hydroxyisophorone being formed in concentrations of 1-50%, depending on the oxidizing agent used. The formation of hydroxyisophorone appears, according to the processes described, to be a secondary reaction. If the course of the reaction is followed, it becomes clear that hydroxy-isophorone is not the intermediate product of 4-oxo-isophorone, as HIP is virtually inert under the oxidation conditions.
The epoxidation of xcex2-isophorone originates with Isler et.al. (Helv. Chim. Acta 39, 1956, 2041 et seq.), who carry out epoxidation with peracetic acid as the oxidizing agent in acetic acid as the solvent and, after changing the pH value to 8-9 with aqueous sodium hydroxide solution, isolate only unsatisfactory yields of HIP. The need to basify with dilute sodium hydroxide solution the solution first obtained, which contains xcex2-IPO, for the production of HIP; gives rise to a stoichiometric salt load (formation of sodium acetate) and prevents recycling of the organic acid. No details are given of the isomerization of xcex2-IP to alpha-isophorone which occurs as a secondary reaction. The yields of HIP from xcex2-IP according to this publication, amount to only about 60%, due to the formation of alpha-IP and the non-selective ring opening of xcex2-IPO to HIP.
The same procedure is described in British patent 791 953, although no details of yields and the formation of by-products are given here. U.S. Pat. No. 2,857,423 by the same authors gives an equally incomplete description of the production of DH-KIP. According to these publications DH-KIP is formed either from HIP by acid catalysis, HIP being produced in a separate reaction and isolated, or from ketoisophorone by partial hydrogenation of the double bond.
Zarghami et al. also (Phytochemistry 10, 1971, 2755 et seq.) do not disclose yields of xcex2-IP epoxide from their reaction with peracetic acid. Tetrahedron Lett. Suppl. No. 8, Pt. 1, 1966, 1-7 gives a further description of the epoxidation of xcex2-isophorone. Organic solvents such as chloroform, using meta-chlorobenzoic acid as the oxidizing agent, are described, m-chlorobenzoic acid being precipitated out from the solution after completion of the redox reaction and a product profile being produced which consists of xcex2-IP epoxide and HIP in a ratio of 1:1, and alpha-isophorone. It is obvious that, according to this process, neither the undesirable re-isomerization to alpha-IP nor the consecutive reaction to HIP can be suppressed. After hydrolysis at a basic pH, 87% HIP is isolated. This procedure is unsatisfactory as the pH environment must be changed several times to produce HIP, which entails a significant salt load and produces only moderate yields.
All of these processes have in common that they produce unsatisfactory yields of xcex2-isophorone epoxide, due to the non-selective reaction process or unsuitable oxidizing agent, or to the presence of water in the reaction medium, which both catalyzes the reverse reaction of xcex2-isophorone and destabilizes the epoxide. The formation of the diol can also be detected from the xcex2-IP epoxide as a result of the accumulation of water.
A further reaction, observed when the reaction is not sufficiently controlled, is the epoxidation of alpha-IP (which is formed in xe2x80x9csituxe2x80x9d from xcex2-IP by isomerization) to alpha-IP epoxide, and its consecutive reaction of isomerization to 2-hydroxyisophorone. These principal secondary reactions are observed also in epoxidation with other substrates, the diols and hydroxyesters being obtained in particular (see W. M. Weigert, Wasserstoffperoxid und seine Derivate [Hydrogen peroxide and its derivatives], Hxc3xcthig Verlag Heidelberg 1978, page 79 et seq.).
The following diagram shows the possible secondary and consecutive reactions of xcex2-IP epoxidation: 
The epoxidation of xcex2-isophorone in the presence of anhydrous peroxidation reagents such as alkylhydroperoxides is also described (Hutter, Baiker et al., Journal Mol. Cat. 172, 427-435, 1997). A heterogenous contact SiO2xe2x80x94TiO2 mixed oxide activates the peroxide, expensive pre-treatment of the catalyst, or the addition of further auxiliary substances such as bases, being necessary to achieve higher selectivities, partly in order to suppress the formation of HIP. Although this process has achieved the best epoxide selectivities hitherto, it is not advantageous to use alkylhydroperoxides, which are spent stoichiometrically, for an industrial process. It is also undesirable to use a heterogeneous contact, which is costly to prepare.
DP 38 06 835 describes the oxidation of xcex2-IP to HIP by reaction with aqueous hydrogen peroxide in the presence of formic acid. xcex2-IP epoxide is discharged as an intermediate, but a re-isomerization rate in the range 20-35% make the process unattractive from an industrial point of view.
No satisfactory process is described, in particular for the rearrangement of xcex2-isophorone epoxide or a mixture of the xcex2-IPO first obtained by epoxidation and hydroxyisophorone. The process suggested in British patent 791 953 for the rearrangement of HIP to DH-KIP is laborious, as HIP must first be produced from xcex2-IPO by basic hydrolysis in a separate process step. The consecutive reaction with strong acids, as described in Isler et al., Helv. Chem. Acta, (1956), No. 237 page 2041, is as laborious as it is non-selective, as HIP must be provided as a pure substance and rearrangement to DH-KIP in the presence of strong acids entails the formation of trimethylphenols as by-products. A reaction time of 20 h is also a substantial disadvantage of this process.
Hitherto, there has been no known process which allows DH-KIP to be produced using inexpensive, industrially efficient and accessible oxidizing agents and high product selectivity, in particular from a readily available mixture of xcex2-isophorone epoxide and hydroxyisophorone. This is the basis of the objects to be achieved by the invention.
An object of the present invention is to produce dihydro-ketoisophorone (DH-KIP) from xcex2-isophorone with high selectivity and yield, suppressing in particular the re-isomerization of the educt to alpha-isophorone, to avoid having to separate alpha-IP from the product solution by expensive means and having to change the environment from acid (environment for epoxidation with organic percarboxylic acids) to basic (prior art for the production of HIP from xcex2-IPO) and back to acid (prior art for rearrangement of HIP to DH-KIP). Furthermore a process is to be provided, which makes it possible to convert the mixture of xcex2-IPO and HIP obtained xe2x80x9cin situxe2x80x9d directly to DH-KIP and to reduce considerably the long reaction times in the prior art.
A further object of the invention is to provide a process for converting xcex2-isophorone epoxide to DH-KIP, xcex2-isophorone epoxide with its isomer hydroxyisophorone being produced from xcex2-isophorone in a first reaction step by reaction with an organic peracid.
The above and other objects can be achieved in that xcex2-isophorone is brought into contact at moderate temperatures with an organic percarboxylic acid dissolved in an organic solvent, the organic solvent being at the same time the extracting agent used to extract the organic peracid as it is produced, and the xcex2-IPO thus obtained together with its isomer hydroxyisophorone which is present as a by-product in a concentration of 0.1-80 mol % (in relation to xcex2-IPO) is isomerized to DH-KIP by thermal isomerization in the presence of the organic carboxylic acid or by reaction in the presence of a salt as catalyst.
According to the process, inexpensive raw materials such as aqueous hydrogen peroxide, organic carboxylic acids and a solvent on the one hand and, in the simplest case, alkali-or earth alkali salts on the other, can be used, and as only the educt substrate xcex2-isophorone and hydrogen peroxide are spent during the epoxidation process, the majority of the other raw materials can be recycled. The catalysts used for the isomerization of xcex2-IPO/HIP solutions can also be recycled and in this sense are not specific consumption materials.
The first aspect of the invention relates to a new process for the production of dihydroketoisophorone by epoxidation of xcex2-isophorone (xcex2-IP) by reaction with a peracid in the form of its solution in a suitable solvent in the liquid phase, which is stable under reaction conditions, thus substantially avoiding separation into two phases which can occur if there is a high concentration of water in the reaction mixture, and obtaining a mixture of organic carboxylic acid, extracting agent (=solvent), xcex2-isophorone epoxide with hydroxyisophorone as the product solution. In the simplest form of the process according to the invention, the solvent used for oxidation is also the agent for extracting the corresponding peracid as it is produced from an aqueous hydrogen peroxide solution, carboxylic acid and sulfuric acid.
The second aspect of the process according to the invention relates to the rearrangement of the xcex2-IPO formed in xe2x80x9csituxe2x80x9d, which, depending on the production process, may contain 0.1-80 mol % hydroxyisophorone, by direct thermal isomerization of the solution obtained from epoxidation or isomerization of the epoxidation solution obtained directly from the reaction in the presence of an additional catalyst salt, in the simplest case an alkali- or earth alkali salt or other suitable isomerization catalysts, or by isomerization of an epoxidation solution, the majority of which at least is first released from the carboxylic acid by extraction or distillation.
To achieve high selectivity, the reaction is carried out in two temperature stages.